One long-range objective of this research program is the synthesis of biologically and structurally interesting alkaloids. A second objective is the development and evaluation of methodology for the synthesis of nitrogen-containing compounds. A third objective is the discovery of biological activities associated with new nitrogen-containing organic compounds. One specific goal of this project is to continue and complete syntheses of manzamine A (1) and ircinal A (2), alkaloids of marine origin reported to have potent antitumor activity. This is to be accomplished using either macrolactamization or olefin metathesis chemistry. As part of this project, a new route to perhydroisoquinolines will be examined, with the goal being the development of a convergent route to synthetic intermediates already in hand. Selected compounds prepared during this venture are to be submitted for evaluation in biological screens related to cancer, viral, cardiovascular, gastrointestinal and CNS disorders. Another specific goal of this project is to initiate and complete a synthesis of gelsedine (3), a major alkaloid component of the plant gelsemium elegans. The route is designed to examine the scope of oxindole chemistry developed during the course of a completed synthesis of gelsemine. Selected synthetic intermediates will again be submitted for evaluation in the aforementioned biological screens.